Neuropilin
Crystallographic structure of the dimeric B1 domain of human neuropilin 1. [1]
Identifiers
Symbol	NRP
InterPro	IPR014648
Membranome	16

Neuropilin is a protein receptor active in neurons.

There are two forms of Neuropilins, NRP-1 and NRP-2. Neuropilins are transmembrane glycoproteins, first documented to regulate neurogenesis and angiogenesis by complexing with Plexin receptors/class-3 semaphorin ligands and Vascular Endothelial Growth Factor (VEGF) receptors/VEGF ligands, respectively. ^{[2] [3]} Neuropilins predominantly act as co-receptors as they have a very small cytoplasmic domain and thus rely upon other cell surface receptors to transduce their signals across a cell membrane. ^{[2] [3]} Recent studies have shown that Neuropilins are multifunctional and can partner with a wide variety of transmembrane receptors. Neuropilins are therefore associated with numerous signalling pathways including those activated by Epidermal Growth Factor (EGF), Fibroblast Growth Factor (FGF), Hepatocyte Growth Factor (HGF), Insulin-like Growth Factor (IGF), Platelet Derived Growth Factor (PDGF) and Transforming Growth Factor beta (TGFβ). ^{[4] [5]} Although Neuropilins are commonly found at the cell surface, they have also been reported within the mitochondria and nucleus. ^{[6] [7]} Both Neuropilin family members can also be found in soluble forms created by alternative splicing or by ectodomain shedding from the cell surface. ^{[8] [9]}

The pleiotropic nature of the NRP receptors results in their involvement in cellular processes, such as axon guidance and angiogenesis, the immune response and remyelination. ^[10] Therefore, dysregulation of NRP activity has been implicated in many pathological conditions, including many types of cancer and cardiovascular disease. ^{[11] [12] [13] [14]}

Applications

Neuropilin-1 is a therapeutic target protein in the treatment for leukemia and lymphoma, since It has been shown that there is increased expression in neuropilin-1 in leukemia and lymphoma cell lines. ^[15] Also, antagonism of neuropilin-1 has been found to inhibit tumour cell migration and adhesion. ^[16]

Structure

Neuropilins contain the following four domains:

• N-terminal CUB domain (for complement C1r/C1s, Uegf, Bmp1)
• Coagulation factor 5/8 type, C-terminal ( discoidin domain)
• MAM domain (for meprin, A-5 protein, and receptor protein-tyrosine phosphatase mu)
• C-terminal neuropilin

The structure of B1 domain (coagulation factor 5/8 type) of neuropilin-1 was determined through X-Ray Diffraction with a resolution of 2.90 Å. The secondary structure of this domain is 5% alpha helical and 46% beta sheet. ^[1]

Ramachandran plot. ^[17]

References

External links

• Neuropilins at the U.S. National Library of Medicine Medical Subject Headings (MeSH)